[unreadable] It is crucial and advantageous if tumors under therapy can be functionally monitored and imaged at different treatment stages. A non-invasive, portable, cost-effective, in vivo imaging tool is much needed to choose, guide and follow cancer therapy. The overall objective of this phased proposal is to develop such a novel imaging modality by utilizing Near Infrared (NIR) tomography in combination with hemodynamic modeling to functionally obtain hemodynamic images of animal brain tumors, which are under radio-surgery with and without respiratory interventions. The tomographic images of changes in hemoglobin concentrations, blood flow, and oxygen consumption rate of the brain tumor caused by different radiation doses in radio-surgery along with hyperoxic interventions can be obtained non-invasively and chronically. Such hemodynamic images may provide prognostic information, for clinical radio-surgery practice, on inhomogeneous responses of the tumor to the therapy and intervention as well as on the effectiveness of the therapy. There are three specific aims in the R21 phase: (1) to design and implement an 8-source, 8- detector, NIR spectroscopic imager suitable for dynamic rat brain imaging of oxygenated hemoglobin concentration and total hemoglobin concentration (HbO, HbT), (2) to develop a 2D tomographic reconstruction algorithm and to obtain 2D dynamic tomography of vascular oxygenation under different oxygen interventions using rat brain tumor phantoms, and (3) to develop and validate, through hemodynamic phantom experiments, mathematical models to quantitatively associates the blood flow (BF) and oxygen consumption rate (O2CR) of the tumor to its HbO and HbT determined by the NIR spectroscopic measurements. After success of the initial R21 development, three specific aims in the R33 phase are: (1) to validate 2D tomographic images of the BF and O2CR using dynamic tumor phantoms, (2) to obtain dynamic images of respiratory-induced changes in HbO, HbT, BF, and O2CR from rat brain tumors (9L Gliosarcoma) before and after radiation therapy with and without carbogen intervention during radiation, and (3) to investigate heterogeneous response of the brain tumors to the intervention and to the radio surgery and to examine the prognostic value of the hemodynamic parameters (Hb, HbO, BF, and O2CR) for the radiation therapy by comparing with the histological analysis of the corresponding tumors. [unreadable] [unreadable]